Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, F-75005, France.
Present address: Institut Pasteur, Bioinformatics and Biostatistics Hub, C3BI, USR 3756 IP CNRS, Paris, France.
Genome Biol. 2017 Oct 31;18(1):207. doi: 10.1186/s13059-017-1333-9.
Polycomb Repressive Complexes 2 (PRC2) are multi-protein chromatin modifiers that are evolutionarily conserved among eukaryotes and play key roles in the regulation of gene expression, notably through the trimethylation of lysine 27 of histone H3 (H3K27me3). Although PRC2-mediated gene regulation has been studied in many organisms, few studies have explored in depth the evolutionary conservation of PRC2 targets.
Here, we compare the H3K27me3 epigenomic profiles for the two closely related species Arabidopsis thaliana and Arabidopsis lyrata and the more distant species Arabis alpina, three Brassicaceae that diverged from each other within the past 24 million years. Using a robust set of gene orthologs present in the three species, we identify two classes of evolutionarily conserved PRC2 targets, which are characterized by either developmentally plastic or developmentally constrained H3K27me3 marking across species. Constrained H3K27me3 marking is associated with higher conservation of promoter sequence information content and higher nucleosome occupancy compared to plastic H3K27me3 marking. Moreover, gene orthologs with constrained H3K27me3 marking exhibit a higher degree of tissue specificity and tend to be involved in developmental functions, whereas gene orthologs with plastic H3K27me3 marking preferentially encode proteins associated with metabolism and stress responses. In addition, gene orthologs with constrained H3K27me3 marking are the predominant contributors to higher-order chromosome organization.
Our findings indicate that developmentally plastic and constrained H3K27me3 marking define two evolutionarily conserved modes of PRC2-mediated gene regulation that are associated with distinct selective pressures operating at multiple scales, from DNA sequence to gene function and chromosome architecture.
多梳抑制复合物 2（PRC2）是一种多蛋白染色质修饰物，在真核生物中具有进化保守性，在基因表达调控中发挥着关键作用，特别是通过组蛋白 H3 赖氨酸 27 的三甲基化（H3K27me3）。尽管 PRC2 介导的基因调控已在许多生物中进行了研究，但很少有研究深入探讨 PRC2 靶标的进化保守性。
在这里，我们比较了两个密切相关的物种拟南芥和拟南芥以及更远缘的物种山芥的 H3K27me3 表观基因组图谱，这三个物种属于过去 2400 万年从彼此分化的十字花科植物。使用在这三个物种中都存在的一组稳健的基因直系同源物，我们确定了两类进化保守的 PRC2 靶标，它们的特征是在物种间具有发育可塑性或发育受限的 H3K27me3 标记。与发育可塑性的 H3K27me3 标记相比，受限的 H3K27me3 标记与启动子序列信息含量的更高保守性和更高核小体占有率相关。此外，具有受限 H3K27me3 标记的基因直系同源物表现出更高的组织特异性，并倾向于参与发育功能，而具有发育可塑性的 H3K27me3 标记的基因直系同源物则优先编码与代谢和应激反应相关的蛋白质。此外，具有受限 H3K27me3 标记的基因直系同源物是高级染色体组织的主要贡献者。
我们的研究结果表明，发育可塑性和受限的 H3K27me3 标记定义了 PRC2 介导的基因调控的两种进化保守模式，这些模式与在多个尺度上（从 DNA 序列到基因功能和染色体结构）作用的不同选择压力相关。
